Chlamydia trachomatis is responsible for a significant proportion of pelvic inflammatory disease (PID) in women. Often chlamydial PID goes unrecognized, yet infection leads to significant sequelae, including adverse pregnancy outcome and obstructive infertility. Chlamydia have been difficult to culture from women with upper genital tract disease, especially after the disease process has become chronic, but evidence is accumulating to indicate that chlamydial genomes continue to be present in diseased upper genital tract tissue of the endometrium and fallopian tubes. We propose that C. trachomatis is present in a culture negative state during these disease processes and can persist within host cells of the genital tract in an atypical form, for prolonged periods of time. We further propose that the particular characteristics of these atypical, persistent chlamydia actually contribute to the disease process by eliciting inflammation and/or delayed type hypersensitivity responses. Our hypothesis is that inflammatory and/or immune-regulated cytokines alter chlamydial host cells in a way that causes persistent chlamydia to develop and that understanding the biochemical attributes of persistent chlamydia will help to better understand the complicated pathogenesis of chronic upper genital tract disease in women. It is not clear if chlamydia can maintain a presence in cells other than the genital epithelium, but as a starting point we propose to study cytokine-mediated changes in polarized human endometrial epithelial cells that may lead to chlamydial persistence, characterize persistent chlamydia at the structural and biochemical level and determine how these atypical organisms may contribute to the disease process and cause upper genital tract infections to be difficult to recognize and manage appropriately.